Although Streptococcus pneumoniae is traditionally considered the preponderant bacterial pathogen in children with nephrotic syndrome, recent data suggest an increase of infections with encapsulated gram-negative organisms. We report two children with idiopathic nephrotic syndrome in relapse who developed spontaneous Escherichia coli cellulitis. The organism was recovered from the cellulitis tissue aspirate of one, and from the blood of the other. Both patients responded to appropriate antibiotic therapy. Initial treatment of sepsis, peritonitis or spontaneous cellulitis in nephrotic patients should include broad spectrum antibiotic coverage pending results of appropriate cultures.